scholarly journals Performance of recurrent event models on defect proneness data

2020 ◽  
Author(s):  
M. K. Lintu ◽  
Asha Kamath
Keyword(s):  
Clinical Trials ◽  
Survival Analysis ◽  
Quality Assessment ◽  
Recurrent Events ◽  
Epidemiological Studies ◽  
Recurrent Event ◽  
Repeated Events ◽  
Module Size ◽  
Event Models ◽  
The Impact

AbstractThe repeated occurrence of the same event in a process is commonly observed in many domains. Such events are referred to as recurrent events. The time to occurrence of these repeated events varies from unit to unit with a possibility of events not occurring among some of the units. Invariably such data are dealt with using some of the techniques in survival analysis called recurrent event models, which are commonly encountered in epidemiological studies and clinical trials. However, it applies to other domains in science and technology. We illustrate the usefulness of recurrent event models in the context of defect proneness analysis in quality assessment of software. Some of the models in practice are introduced on data collected to study the impact of module size on defect proneness in the Mozilla product. Module size plays a significant role in defect proneness and each defect fix makes the class more susceptible to further defects. The risk estimates obtained from the different models vary owing to the differences in the properties of the models as well as the assumptions underlying it.

scholarly journals Comparison of Time-to-First Event and Recurrent-Event Methods in Randomized Clinical Trials

Circulation ◽  
2018 ◽  
Vol 138 (6) ◽  
pp. 570-577 ◽  
Author(s):  
Brian Claggett ◽  
Stuart Pocock ◽  
L.J. Wei ◽  
Marc A. Pfeffer ◽  
John J.V. McMurray ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Statistical Power ◽  
Recurrent Events ◽  
Randomized Clinical Trials ◽  
Cox Model ◽  
Study Drug ◽  
Recurrent Event ◽  
Drug Discontinuation ◽  
Patient Heterogeneity ◽  
Study Drug Discontinuation

Background: Most phase-3 trials feature time-to-first event end points for their primary and secondary analyses. In chronic diseases, where a clinical event can occur >1 time, recurrent-event methods have been proposed to more fully capture disease burden and have been assumed to improve statistical precision and power compared with conventional time-to-first methods. Methods: To better characterize factors that influence statistical properties of recurrent-event and time-to-first methods in the evaluation of randomized therapy, we repeatedly simulated trials with 1:1 randomization of 4000 patients to active versus control therapy, with true patient-level risk reduction of 20% (ie, relative risk=0.80). For patients who discontinued active therapy after a first event, we assumed their risk reverted subsequently to their original placebo-level risk. Through simulation, we varied the degree of between-patient heterogeneity of risk and the extent of treatment discontinuation. Findings were compared with those from actual randomized clinical trials. Results: As the degree of between-patient heterogeneity of risk increased, both time-to-first and recurrent-event methods lost statistical power to detect a true risk reduction and confidence intervals widened. The recurrent-event analyses continued to estimate the true relative risk (0.80) as heterogeneity increased, whereas the Cox model produced attenuated estimates. The power of recurrent-event methods declined as the rate of study drug discontinuation postevent increased. Recurrent-event methods provided greater power than time-to-first methods in scenarios where drug discontinuation was ≤30% after a first event, lesser power with drug discontinuation rates of ≥60%, and comparable power otherwise. We confirmed in several actual trials of chronic heart failure that treatment effect estimates were attenuated when estimated via the Cox model and that increased statistical power from recurrent-event methods was most pronounced in trials with lower treatment discontinuation rates. Conclusions: We find that the statistical power of both recurrent-events and time-to-first methods are reduced by increasing heterogeneity of patient risk, a parameter not included in conventional power and sample size formulas. Data from real clinical trials are consistent with simulation studies, confirming that the greatest statistical gains from use of recurrent-events methods occur in the presence of high patient heterogeneity and low rates of study drug discontinuation.

scholarly journals Left-censored recurrent event analysis in epidemiological studies: a proposal for when the number of previous episodes is unknown

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Gilma Hernández-Herrera ◽  
David Moriña ◽  
Albert Navarro
Keyword(s):  
At Risk ◽  
Recurrent Events ◽  
Counting Process ◽  
Frailty Model ◽  
R Package ◽  
Epidemiological Studies ◽  
Recurrent Event ◽  
Event Analysis ◽  
Gap Time

Abstract Background When dealing with recurrent events in observational studies it is common to include subjects who became at risk before follow-up. This phenomenon is known as left censoring, and simply ignoring these prior episodes can lead to biased and inefficient estimates. We aimed to propose a statistical method that performs well in this setting. Methods Our proposal was based on the use of models with specific baseline hazards. In this, the number of prior episodes were imputed when unknown and stratified according to whether the subject had been at risk of presenting the event before t = 0. A frailty term was also used. Two formulations were used for this “Specific Hazard Frailty Model Imputed” based on the “counting process” and “gap time.” Performance was then examined in different scenarios through a comprehensive simulation study. Results The proposed method performed well even when the percentage of subjects at risk before follow-up was very high. Biases were often below 10% and coverages were around 95%, being somewhat conservative. The gap time approach performed better with constant baseline hazards, whereas the counting process performed better with non-constant baseline hazards. Conclusions The use of common baseline methods is not advised when knowledge of prior episodes experienced by a participant is lacking. The approach in this study performed acceptably in most scenarios in which it was evaluated and should be considered an alternative in this context. It has been made freely available to interested researchers as R package miRecSurv.

Glutamate theory of depression-new elements

2011 ◽  
Vol 26 (S2) ◽  
pp. 1261-1261
Author(s):  
A.G. Mititelu
Keyword(s):  
Clinical Trials ◽  
Drug Dependence ◽  
Pharmaceutical Compounds ◽  
Epidemiological Studies ◽  
The Other ◽  
Nmda Antagonists ◽  
Site Of Action ◽  
Putative Site ◽  
Chemical Products ◽  
The Impact

IntroductionIt is well known that actual mechanisms which explain depression are very exhaustive and at same time extremely limited. Among these ones, it had been given the priority, maybe too quick, to serotonin hypothesis. Even so, the actual SSRI and SRNI classes doesn’t do. really, a lot in alleviating the course of the disease. Recent randomised clinical trials and clinic -epidemiological studies support the idea that something more effective must be offered. On the other side addiction reveals more and more in depth correlations with all major psychiatric disorders.ObjectivesIt is possible to develop in the close future new chemical products which could act in more effective way for the reduction or even cancelling of the symptoms determined by the alteration of major neurotransmitters-, GABA and glutamate.AimsBased on huge interconnection which exists between depression and drug dependence at various levels-especially through the effects exerted by particular anti depressant and some of anti craving medications, it is possible to evaluate the impact which some new pharmaceutical compounds -derivated from glutamate type of receptor NMDA-might exert upon various types of depression elicited by patients with associated drug dependence.MethodsHad been realised a thematical reanalysis of the studies published on Medline, EMBASE and OVID about this subject.ResultsThe conclusion of the studies reveals the huge potential represented by treatment with some types of NMDA antagonists-Ketamine. The putative site of action is prefrontal cortex and is had been proved highly efficient in MDD patients.

scholarly journals Omega 3 Fatty Acids and Neurodegenerative Diseases: New Evidence in Clinical Trials

2019 ◽  
Author(s):  
Rossella Avallone ◽  
Giovanni Vitale ◽  
Marco Bertolotti
Keyword(s):  
Fatty Acids ◽  
Clinical Trials ◽  
Neurodegenerative Diseases ◽  
Epidemiological Studies ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Beneficial Effects ◽  
Cell Membrane Fluidity ◽  
The Impact ◽  
New Evidence

A nutritional approach could be a promising strategy to prevent or slow the progression of neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease, since there is no effective therapy for these diseases so far. The beneficial effects of omega-3 fatty acids are now well established by a plethora of studies through their involvement in multiple biochemical functions, including synthesis of antinflammatory mediators, cell membrane fluidity, intracellular signalling and gene expression. This systematic review will consider epidemiological studies and clinical trials that assessed the impact of supplementation or dietary intake of omega-3 polyunsaturated fatty acids on neurodegenerative diseases such as Parkinson’s and Alzheimer’s diseases. Indeed, treatment with omega-3 fatty acids, being safe and well tolerated, represent a valuable and biologically plausible tool in the management of neurodegenerative diseases in their early stages.

Abstract TP410: Race/ethnicity Modifies Increased Recurrent Event Risk For Female Stroke Survivors

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Emma K Benn ◽  
Kezhen Fei ◽  
Eric T Roberts ◽  
Leigh Quarles ◽  
Bernadette Boden-Albala
Keyword(s):  
Health Status ◽  
Recurrent Events ◽  
Medical Center ◽  
Recurrent Event ◽  
Stroke Survivors ◽  
Functional Scores ◽  
Race Ethnicity ◽  
The Difference ◽  
Stroke Mimic ◽  
The Impact

INTRODUCTION: Demographic disparities in recurrent events among stroke survivors have received some attention, but little is known about the impact of gender. We explored whether gender was associated with having a recurrent event, after accounting for health status and SES, in a multi-ethnic stroke cohort. METHODS: The Stroke Warning Information and Faster Treatment study (SWIFT) was a randomized stroke preparedness educational intervention, which prospectively enrolled mild and moderate stroke/TIA patients able to sign informed consent and identified at the NY Presbyterian Medical Center from 2005 to 2010. We defined a recurrent event as having ≥1 of the following post-enrollment: a stroke, TIA, MI, death, migraine, or significant stroke mimic. Gender was dichotomous. Health status included age, race/ethnicity, comorbidities, and CVD history. SES included education, employment, and insurance. We conducted chi-squared tests and t-tests. We used multiple logistic regression to assess the impact of gender, after adjustment for health status and SES, on having a recurrent event. Effect modification of the adjusted gender difference by race/ethnicity was also examined. RESULTS: The cohort included 1203 patients, of which 31% (n=375) had 580 recurrent events. Intervention was not associated with gender (p=0.35) nor having a recurrent event (p=0.07). Females (n=596, 49.5%) were older (p=0.002), had a higher proportion of comorbid hypertension (p=0.019), had less non-Hispanic Whites (p=0.028), were less educated (p=0.022), and had more Medicaid recipients (p<0.001), than males. About 35% of females and 28% of males had a recurrent event (p=0.006). The adjusted odds of a recurrent event were 1.35-fold (95% CI=1.04-1.75) higher for females than for males. Race/ethnicity modified the association. Females, compared to males, were similar for Blacks (OR=1.26, 95% CI=0.68-2.33) and Latinos (OR=0.87, 95% CI=0.60-1.24), yet the difference was substantial among Whites (OR=3.16, 95% CI=1.84-5.41). CONCLUSION: While age has historically been suggested as an explanation for poorer functional scores post stroke, the nature of these recurrent events among women with milder stroke/TIA and its intersection with race/ethnicity needs further exploration.

scholarly journals The Monitoring and Evaluation of a Multicountry Surveillance Study, the Severe Typhoid Fever in Africa Program

2019 ◽  
Vol 69 (Supplement_6) ◽  
pp. S510-S518
Author(s):  
Ondari D Mogeni ◽  
Ligia María Cruz Espinoza ◽  
Justin Im ◽  
Ursula Panzner ◽  
Trevor Toy ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Typhoid Fever ◽  
Monitoring And Evaluation ◽  
Epidemiological Studies ◽  
Limited Information ◽  
Monitoring Methods ◽  
Sustainable Solutions ◽  
Preliminary Results ◽  
Monitoring Activities ◽  
The Impact

Abstract Background There is limited information on the best practices for monitoring multicountry epidemiological studies. Here, we describe the monitoring and evaluation procedures created for the multicountry Severe Typhoid Fever in Africa (SETA) study. Methods Elements from the US Food and Drug Administration (FDA) and European Centre for Disease Prevention and Control (ECDC) recommendations on monitoring clinical trials and data quality, respectively were applied in the development of the SETA monitoring plan. The SETA core activities as well as the key data and activities required for the delivery of SETA outcomes were identified. With this information, a list of key monitorable indicators was developed using on-site and centralized monitoring methods, and a dedicated monitoring team was formed. The core activities were monitored on-site in each country at least twice per year and the SETA databases were monitored centrally as a collaborative effort between the International Vaccine Institute and study sites. Monthly reports were generated for key indicators and used to guide risk-based monitoring specific for each country. Results Preliminary results show that monitoring activities have increased compliance with protocol and standard operating procedures. A reduction in blood culture contamination following monitoring field visits in two of the SETA countries are preliminary results of the impact of monitoring activities. Conclusions Current monitoring recommendations applicable to clinical trials and routine surveillance systems can be adapted for monitoring epidemiological studies. Continued monitoring efforts ensure that the procedures are harmonized across sites. Flexibility, ongoing feedback, and team participation yield sustainable solutions.

scholarly journals Omega-3 Fatty Acids and Neurodegenerative Diseases: New Evidence in Clinical Trials

2019 ◽  
Vol 20 (17) ◽  
pp. 4256 ◽  
Author(s):  
Rossella Avallone ◽  
Giovanni Vitale ◽  
Marco Bertolotti
Keyword(s):  
Fatty Acids ◽  
Clinical Trials ◽  
Neurodegenerative Diseases ◽  
Intracellular Signaling ◽  
Epidemiological Studies ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Beneficial Effects ◽  
Cell Membrane Fluidity ◽  
The Impact

A nutritional approach could be a promising strategy to prevent or slow the progression of neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease, since there is no effective therapy for these diseases so far. The beneficial effects of omega-3 fatty acids are now well established by a plethora of studies through their involvement in multiple biochemical functions, including synthesis of anti-inflammatory mediators, cell membrane fluidity, intracellular signaling, and gene expression. This systematic review will consider epidemiological studies and clinical trials that assessed the impact of supplementation or dietary intake of omega-3 polyunsaturated fatty acids on neurodegenerative diseases such as Parkinson’s and Alzheimer’s diseases. Indeed, treatment with omega-3 fatty acids, being safe and well tolerated, represents a valuable and biologically plausible tool in the management of neurodegenerative diseases in their early stages.

scholarly journals Are clinical trial results transferable in the real life?

2016 ◽  
Vol 84 (1-2) ◽  
Author(s):  
Enrico Natale ◽  
Alfiera Marsocci
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Clinical Practice ◽  
Recurrent Events ◽  
Randomized Clinical Trials ◽  
Real Life ◽  
Recurrent Event ◽  
The Real ◽  
Number Of Patients ◽  
Clinical Trial Results

<p>Generally in the clinical practice patients are more complex in comparison with those included in the clinical trials. In this article, we discuss three relevant items, which may implement the transferability of the clinical trial results in the real world. The observational studies have fewer restrictions on the number of patients included, due to more relaxed inclusion and exlusion criteria than in randomized clinical trials. The absence of randomization however may lead to potential for bias. The recurrent event analysis may extend the positive results of clinical trials regarding the reductions of the first primary endpoint event to total events, including those beyond the first event. This analysis is of great interest in the clinical practice, where recurrent events are common. Finally the reliability of subgroup analysis is discussed. Pre-specified subgroup analyses are more credible and valuable than <em>post-hoc</em> analyses.</p><p><strong>Riassunto</strong></p><p>Nella pratica clinica i pazienti sono generalmente più complessi rispetto alle popolazioni studiate nei trial clinici. Si rendono necessari pertanto strumenti di analisi che integrino i trial clinici. In questo articolo vengono esaminati alcuni punti di rilevante importanza nella definizione di una corretta applicabilità dei risultati dei trial clinici al mondo reale. Il primo punto riguarda il ruolo e i limiti degli studi osservazionali. Il secondo tratta delle analisi degli eventi ricorrenti, una modalità di analisi dei trial clinici che rende i risultati più aderenti alla vita reale, nella consapevolezza che limitare i dati di outcome al primo evento sia riduttivo rispetto alla necessità di stabilire che l’intervento studiato nel trial confermi la sua efficacia anche sugli eventi successivi al primo. Il terzo punto riguarda la controversa questione delle analisi per sottogruppi, uno strumento utile per generare ipotesi, ma discutibile quando impiegato per rimediare a trial con risultati negativi o estendere i risultati di trial positivi a sottopopolazioni particolari di pazienti. </p>

Frailty modelling for multitype recurrent events in clinical trials

2018 ◽  
Vol 19 (2) ◽  
pp. 140-156
Author(s):  
Paul M Brown ◽  
Justin A Ezekowitz
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Data Structure ◽  
Recurrent Events ◽  
Clinical Trial Data ◽  
Trial Data ◽  
Recurrent Event ◽  
Review Of The Literature ◽  
Survival Times ◽  
The Past

Recurrent event outcomes are ubiquitous among clinical trial data which encourages a conventional approach to analysis. Yet a common feature of these data has received less attention, that is, survival times often comprise multiple types of events that may imply a disparity in cost and disease severity. Typically, we neglect this feature of the data by combining event-types or analyzing each type separately, thus ignoring any interdependence among them. This practice may reflect a dearth of readily available methods and software that more appropriately acknowledge the true data structure. We provide a review of the literature on multitype recurrent events and frailty modelling which reflects a renewed interest in the topic over the past decade and the emergence of software for estimation. Thus, a review of available methods seems timely, if not overdue.

Sign in / Sign up

Export Citation Format

Share Document